CZ35097A3 - Granulation process of sodium hyaluronate - Google Patents

Abstract

A method of granulating sodium hyaluronate, optionally other inorganic hyaluronic acid salts, It consists in being dried gently ground hyaluronic acid salt is mixed with aqueous solution of branched aliphatic alcohols unbranched chain and one up to six carbon atoms or ketones with one up to four carbon atoms, by volume the amount of organic solvent may be 0.1 to 5 times the amount of hyaluronan, and an amount of water of 0.01 to 0.9 times »The amount of hyaluronan. For the granulation process maybe a hyaluronan mixture, moist after precipitation organic solvent.

Description

Technical field

The invention relates to a process for granulating sodium hyaluronate or other inorganic salts of hyaluronic acid.

BACKGROUND OF THE INVENTION

Previously known granulation methods are carried out by spraying the powdered substance, optionally in admixture with other components, with fine droplets of water, wetting some of the particles of the granular substrate, which are wrapped up on top of each other, thereby finally forming a macroscopic particle particle-granule.

In the case of hyaluronic acid, however, this process is in principle unsuccessful because, due to the nature of the substance, which is typical of polysaccharides, the resulting product is glassy and greyish. This is absolutely unacceptable due to the nature of the application in cosmetics and pharmacy. For this reason, only the powder form of hyaluronans (sometimes inaccurately called hyaluronic acid) has been supplied, which has the disadvantage of high dustiness and due to the formation of agglomerates upon dissolution, a slow dissolution process prior to formulation of the predominant dosage form, which is a solution. Dusting is not only aesthetic or lossy. The hyaluronic acid adhered to the process line apparatus after wetting produces a gel which is highly resistant to conventional cleaning procedures and is also a suitable nutrient medium for the growth of undesirable microorganisms, which is a highly undesirable phenomenon due to the application areas outlined above. ,

SUMMARY OF THE INVENTION

The above mentioned drawbacks are largely eliminated by the method of granulation of sodium hyaluronate or other inorganic salts of hyaluronic acid, which is based on the fact that granulation is achieved by mixing dried, finely ground salt of hyaluronate with an aqueous solution of branched and unbranched aliphatic alcohols and one to one chain. The amount of organic solvent can be 0.1 to 5 times the amount of hyaluronan and the amount of water is 0.01 to 0.9 times the amount of hyaluronan. The granulation process according to the invention is also possible when the hyaluronan mixture is wet after precipitation with an organic solvent.

Hyaluronic acid is a polysaccharide consisting of alternately glucuronic acid and N-acetylglucosamine molecules linked by β- (1-3) and β- (1-4) glycosidic bonds. The molecular weight of the polysaccharides usually ranges from several hundred thousand to several million Da. It is used in cosmetics as a moisturizer, or in pharmacy for the treatment of osteoarthritis and in eye surgery.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

An experimental apparatus was constructed consisting of a duplicate 100 L horizontal stirred vessel equipped with a frame stirrer. The vessel was connected to a condensation system and a vacuum source. 3.5 kg of dry and finely powdered sodium hyaluronate was introduced into the vessel and sprayed onto the surface

4.9 kg of an 80% aqueous ethanol solution. The mixture was stirred at normal temperature and pressure for one hour. Then the vacuum source and the heating of the medium in the jacket were switched on. The final pressure and temperature values were 20 kPa, respectively. 70 ° C. The mixture was dried for 6 hours to a 95% solids. After this time, the mixture was removed from the vessel and sieved on a sieve. Three fractions were collected: above the 1.2 mm particle diameter, a product fraction with a particle size in the range of 1.2 to 0.2 mm, and a fraction below 0.2 mm. The weights of the individual fractions were 4.6%, 89.6% and 5.8% of the product obtained. The product fraction was characterized by easy flowability and non-dustiness. The above and subnet product was recycled.

Example 2

The procedure of Example 1 was repeated except that 6.65 kg of filter cake was taken instead of dry sodium hyaluronan after alcohol precipitation of hyaluronan. The content of anhydrous ethanol in this cake was 48%. 1.75 kg of 44% aqueous ethanol was added to the substrate and the mixture was homogenized by stirring for one hour. It was then dried as above. The fractions were 5.8%, 90.9% and 3.3% respectively.

Example 3

The procedure described in Example 1 was repeated except that a 7: 3 mixture of water and acetone was used to wet the mixture before drying. The yield of the individual fractions was 8.0%,

88.9% and 3.1%, respectively.

Example 4

The procedure described in Example 1 was repeated except that a 8.5: 1 mixture of methyl ethyl ketone and water was used to wet the mixture before drying. The yields of the individual fractions were 3.5%, 84.8% and 11.7% respectively. .

<Example 5

The procedure described in Example 1 was repeated except that a 9: 1 mixture of 2-hexanol and water was used to wet the mixture before drying. The yield of the individual fractions was 2.5%,

83.9% and 13.6%.

Example 6

The procedure described in Example 1 was repeated except that the same amount of potassium hyaluronate was taken instead of sodium hyaluronate. The yields of the individual fractions were 4.3%, 89.4% and 6.3%.

Claims (2)

PATENT CLAIMS Process for granulating sodium hyaluronate or other inorganic salts of hyaluronic acid, characterized in that the granulation is achieved by mixing the dried, finely ground salt of hyaluronic acid with an aqueous solution of branched and unbranched aliphatic alcohols and one to six carbon atoms or ketones with one to four carbon atoms, the volume of organic solvent being 0.1 to 5 times the amount of hyaluronan and the amount of water 0.01 to 0.9 times the amount of hyaluronan. 2. Method for granulating sodium hyaluronate or other inorganic salts of hyaluronic acid according to claim 1, characterized in that a granulation of hyaluronan, which is moist after precipitation with an organic solvent, is possible for granulation.